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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Biological Research Laboratory Ltd., 4414 Fuellinsdorf, Switzerland
- Age at study initiation: 10 (males) / 12 (females) weeks old
- Weight at study initiation: 184.8 - 192.0 g (males) / 183.8 - 195.6 g (females)
- Fasting period before study: no
- Housing: by groups of 5 in makrolon type-4 cages (59 x 38.5 x 20 cm)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3°C
- Humidity: 50 ± 20%
- Air changes: 10 to 15 per hr
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: From 04 January 1993 To 25 January 1993

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: piston/brush-feed aerosol generator (RBG 1000, Palas GmbH, 7500 Karlsruhe 1, Germany)
- Exposure chamber volume: not specified
- Method of holding animals in test chamber: individual macrolon restraining tubes positioned radially around exposure chamber
- Source and rate of air: compressed air at 1.0 L/min/animal
- Method of conditioning air: filtering + Ni63 charge neutralizer
- System of generating particulates/aerosols: piston/stainless steel brush
- Method of particle size determination: aerosol concentration monitored using a RAM-1 light scattering type monitor / particle size distribution determined once during exposure using a Mercer 7 stage cascade impactor
- Treatment of exhaust air: not specified
- Temperature, humidity, oxygene concentration: 22.1°C, 5.0%, 20.9%, respectively


TEST ATMOSPHERE
- Brief description of analytical method used: aerosol concentration monitored by light scattering / particle size distribution determined by cascade impaction
- Samples taken from breathing zone: yes
- Particle size distribution (cumulative %):
< 0.325 µ = 3%
< 0.715 µ = 5.1%
< 1.06 µ = 16.7%
< 1.6 µ = 43.9%
< 2.13 µ = 64.6%
< 3 µ = 85.4%
< 4.6 µ = 94.1%
> 4.6 µ = 100%


- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): Gravimetric concentration used

- Rationale for the selection of the starting concentration: Maximal concentration for a limit test
Analytical verification of test atmosphere concentrations:
yes
Remarks:
aerosol concentration monitored by light scattering
Duration of exposure:
4 h
Concentrations:
5.047 ± 0.93 mg/L air (mean ± SD)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:
Mortality: once per hour during exposure, once after exposure on day 1, twice daily thereafter
Clinical signs: once per hour during exposure, once after exposure on day 1, once daily thereafter
Body weight: before exposure on day 1 and on days 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: lungs, trachea, larynx and nasopharyngeal tissues preserved for histopathology
Statistics:
LOGIT-Model (not applied due to absence of deaths)

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.05 mg/L air (analytical)
Based on:
act. ingr.
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC0
Effect level:
5.05 mg/L air (analytical)
Based on:
act. ingr.
Exp. duration:
4 h
Mortality:
No mortality occurred during the exposure and observation periods
Clinical signs:
other: Labored breathing and ruffled fur were noted in 2 males just after exposure. This persisted in one male for up to 24 hours after exposure.
Body weight:
No significant changes in body weight were seen when compared to controls
Gross pathology:
At necropsy, the lungs of all animals were incompletely collapsed with diffuse whitish foci

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Inhalation LC50 was higher than 5.05 mg/L for male and female rats exposed for 4 hours
Executive summary:

In an acute inhalation toxicity study (RCC Project No. 330974), one group of 10 to 12-week old Wistar rats (5/sex) was exposed by nose-only inhalation route to Cerium Oxide for 4 hours at a mean gravimetric concentration of 5.05 mg/L, and observed for 15 days. Mortality and clinical signs were checked during and just after exposure, and daily for 15 days. Body weight was recorded prior to exposure and on days 8 and 15.

 

No mortality occurred during the exposure and observation periods. Labored breathing and ruffled fur were noted in 2 males just after exposure. This persisted in one male for up to 24 hours after exposure. No significant changes in body weight were seen when compared to controls. At necropsy, the lungs of all animals were incompletely collapsed with diffuse whitish foci.

 

Therefore, the inhalation LC50 was higher than 5.05 mg/L for males and females exposed for 4 hours. No classification for acute inhalation toxicity is warranted based on the absence of mortality at the concentration tested, according to the criteria of Annex VI Directive 67/548/EEC or UN/EU GHS.

 

This study is classified as acceptable. It satisfies the OECD 403 guideline requirements for acute inhalation toxicity.